The AST:ALT ratio is most useful when monitoring a clinical condition and may not be applicable in the absence of acute illness, cerebrovascular or metabolic dysfunction, liver disease, or muscle damage despite normal or optimal AST and ALT levels.
The AST:ALT ratio, also known as the De Ritis ratio, had primarily been utilized to monitor progression and severity of liver disease, although its clinical utility has expanded since it was first established. It is not considered a stand-alone diagnostic tool and should be evaluated over time, along with clinical presentation and laboratory assessment.
Though evaluation of the ratio can be complex (Botros 2013), in general the AST:ALT ratio may become elevated in cirrhosis, muscle damage, biliary obstruction, and Wilson’s disease (Gowda 2009, Hall 2012, Rief 2016, Thap 2007), critical limb ischemia (Woreta 2014), and poor stroke outcome (Gao 2017). An increased AST:ALT ratio has also been observed with more severe and fatal COVID-19 versus survivors, even if individual AST and ALT levels didn’t differ significantly between survivors and non-survivors (Zinellu 2021).
The AST:ALT ratio maintains a negative correlation with the components of metabolic syndrome, especially central obesity, and will be lowest in those with the greatest risk of metabolic syndrome (Hanley 2005). These individuals will then have an elevated ALT:AST ratio.
If AST and ALT are optimal and there is no historical or clinical evidence of muscle damage, liver dysfunction, metabolic syndrome, stroke, or other acute illness, an abnormal ratio may not have clinical significance.
However, there may be pathological conditions in which an elevated ratio has clinical significance despite AST and ALT being within standard or even optimal range. One retrospective study of 421 acute ischemic stroke patients found that those with the poorest outcome had the highest AST:ALT ratio. Researchers note that a baseline ratio of greater than 1.53 was independently associated with a 1.89-fold greater risk of poor outcome at 3 months. Interestingly, those with the highest AST:ALT and poorest prognosis had the lowest median levels of AST and ALT at 18.1 IU/L and 15.7 IU/L respectively, levels that are within optimal range. Researchers note that both AST and ALT may be neuroprotective and help reduce the circulating glutamate that increases following a stroke (Gao 2017).
References
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Gao, Fan et al. “De Ritis ratio (AST/ALT) as an independent predictor of poor outcome in patients with acute ischemic stroke.” Neuropsychiatric disease and treatment vol. 13 1551-1557. 15 Jun. 2017, doi:10.2147/NDT.S139316
Gowda S, Desai PB, Hull VV, et al. A review on laboratory liver function tests. Pan Afr Med J. 2009 Nov 22;3:17.
Hall P, Cash J. What is the real function of the liver 'function' tests? Ulster Med J. 2012 Jan;81(1):30-6.
Hanley AJ, Williams K, Festa A, et al. Liver markers and development of the metabolic syndrome: the insulin resistance atherosclerosis study. Diabetes. 2005 Nov;54(11):3140-7.
Newsome PN, Cramb R, Davison SM, et al. Guidelines on the management of abnormal liver blood tests. Gut. 2018 Jan;67(1):6-19.
Rief P, Pichler M, Raggam R, et al. The AST/ALT (De-Ritis) ratio: A novel marker for critical limb ischemia in peripheral arterial occlusive disease patients. Medicine (Baltimore). 2016 Jun;95(24):e3843.
Thapa, B R, and Anuj Walia. “Liver function tests and their interpretation.” Indian journal of pediatrics vol. 74,7 (2007): 663-71. doi:10.1007/s12098-007-0118-7
Woreta TA, Alqahtani SA. Evaluation of abnormal liver tests. Med Clin North Am. 2014 Jan;98(1):1-16.
Zinellu, Angelo et al. “The De Ritis ratio as prognostic biomarker of in-hospital mortality in COVID-19 patients.” European journal of clinical investigation vol. 51,1 (2021): e13427. doi:10.1111/eci.13427